Ammonia → N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamide

HRID 651702Notes

Reaction equation

HRID 651702 reaction equation
[Ca].N.C([N:10]1[C:18]2[C:13](=[CH:14][C:15]([CH2:19][S:20]([N:23](C(C3C=CC=CC=3)C3C=CC=CC=3)[CH3:24])(=[O:22])=[O:21])=[CH:16][CH:17]=2)[C:12]([CH2:38][C@H:39]2[CH2:43][CH2:42][CH2:41][N:40]2[CH3:44])=[CH:11]1)C1C=CC=CC=1.[Cl-].[NH4+]>O1CCCC1.O>[CH3:24][NH:23][S:20]([CH2:19][C:15]1[CH:14]=[C:13]2[C:18](=[CH:17][CH:16]=1)[NH:10][CH:11]=[C:12]2[CH2:38][C@H:39]1[CH2:43][CH2:42][CH2:41][N:40]1[CH3:44])(=[O:21])=[O:22]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 5460341CalciumHCID 57119402(R)-1-[1-benzyl-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]-N-diphenylmethyl-N-methylmethanesulfonamide

Product 1

HCID 132552N-Methyl-3-(((2R)-1-methyl-2-pyrrolidinyl)methyl)-1H-indole-5-methanesulfonamideYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Into a stirred slurry of calcium tunings (1.11 g, 27.7 mmol) in tetrahydrofuran (1.2 ml) at −40° C. was added condensed liquid ammonia (16 ml). The blue bronze was stirred at −50 to −40° C. for a further 15 min, before a solution of (R)-1-[1-benzyl-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indol-5-yl]-N-diphenylmethyl-N-methylmethanesulfonamide (from step (e), 4.0 g, 6.93 mmol) in tetrahydrofuran (10 ml) was added dropwise, maintaining the temperature below −40° C. The dark blue solution was stirred at −40° C. for a further 30 min, before saturated ammonium chloride solution (10 ml) was added dropwise and the grey solution warmed to ambient temperature. Water (10 ml) was then added and the white slurry stirred for 15 min, before being filtered in vacuo. The solid was then dissolved in 5N HCl (12 ml) and the resulting orange solution extracted with ethyl acetate (10 ml). The pH of the aqueous phase was then adjusted (pH=10) with 10N NaOH which resulted in precipitation. The solid was filtered and dried in vacuo at 50° C. overnight to yield the title compound (1.54 g, 73%) as a white solid. m.p. 209-212° C.

Workup

  1. additionwas added dropwise
  2. temperaturemaintaining the temperature below −40° C
  3. additionwas added dropwise
  4. filtrationbefore being filtered in vacuo
  5. dissolutionThe solid was then dissolved in 5N HCl (12 ml)
  6. extractionthe resulting orange solution extracted with ethyl acetate (10 ml)
  7. customresulted in precipitation
  8. filtrationThe solid was filtered
  9. customdried in vacuo at 50° C. overnight

Sources & evidence

ORD record
ord-0870a351c85144a7a1df8627e2a8a342
Source dataset
uspto-grants-2001_08
Patent number
US06281357B1

Reaction notes

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